Kidney transplant recipients (KTRs) are extremely vulnerable to SARS‐CoV‐2 infection and show an impaired immune response to SARS‐CoV‐2 vaccination. We analyzed factors related to vaccination ...efficiency in KTRs. In a multicenter prospective observational study (NCT04743947), IgG antibodies levels against SARS‐CoV‐2 spike S1 subunit and their neutralization capacity after SARS‐CoV‐2 vaccination were analyzed in 225 KTRs and compared to 176 controls. After the vaccination, 56 (24.9%) KTRs became seropositive of whom 68% had neutralizing antibodies. This immune response was significantly lower compared to controls (239 78–519 BAU/ml versus 1826 560–3180 BAU/ml for KTRs and controls, p < .0001). The strongest predictor for an impaired response was mycophenolate mofetil (MMF) treatment. Multivariate regression analysis revealed that MMF‐free regimen was highly associated with seroconversion (OR 13.25, 95% CI 3.22–54.6; p < .001). In contrast, other immunosuppressive drugs had no significant influence. 187 out of 225 KTRs were treated with MMF of whom 26 (13.9%) developed antibodies. 23 of these seropositive KTRs had a daily MMF dose ≤1 g. Furthermore, higher trough MMF concentrations correlated with lower antibody titers (R −0.354, p < .001) supporting a dose‐dependent unfavorable effect of MMF. Our data indicate that MMF dose modification could lead to an improved immune response.
The study examines the dose dependent negative effect of mycophenolate mofetil on the observed poor immune response to COVID‐19 vaccination in kidney transplant recipients.
Kidney transplant recipients (KTR) may be at increased risk of adverse COVID‐19 outcomes, due to prevalent comorbidities and immunosuppressed status. Given the global differences in COVID‐19 policies ...and treatments, a robust assessment of all evidence is necessary to evaluate the clinical course of COVID‐19 in KTR. Studies on mortality and acute kidney injury (AKI) in KTR in the World Health Organization COVID‐19 database were systematically reviewed. We selected studies published between March 2020 and January 18th 2021, including at least five KTR with COVID‐19. Random‐effects meta‐analyses were performed to calculate overall proportions, including 95% confidence intervals (95% CI). Subgroup analyses were performed on time of submission, geographical region, sex, age, time after transplantation, comorbidities, and treatments. We included 74 studies with 5559 KTR with COVID‐19 (64.0% males, mean age 58.2 years, mean 73 months after transplantation) in total. The risk of mortality, 23% (95% CI: 21%–27%), and AKI, 50% (95% CI: 44%–56%), is high among KTR with COVID‐19, regardless of sex, age and comorbidities, underlining the call to accelerate vaccination programs for KTR. Given the suboptimal reporting across the identified studies, we urge researchers to consistently report anthropometrics, kidney function at baseline and discharge, (changes in) immunosuppressive therapy, AKI, and renal outcome among KTR.
This systematic review and meta‐analysis on COVID‐19 in kidney transplant recipients reveals high global mortality rates and provides recommendations for reporting of studies in future pandemics.
Although cold ischemia time has been widely studied in renal transplantation area, there is no consensus on its precise relationship with the transplantation outcomes. To study this, we sampled data ...from 3839 adult recipients of a first heart-beating deceased donor kidney transplanted between 2000 and 2011 within the French observational multicentric prospective DIVAT cohort. A Cox model was used to assess the relationship between cold ischemia time and death-censored graft survival or patient survival by using piecewise log-linear function. There was a significant proportional increase in the risk of graft failure for each additional hour of cold ischemia time (hazard ratio, 1.013). As an example, a patient who received a kidney with a cold ischemia time of 30h presented a risk of graft failure near 40% higher than a patient with a cold ischemia time of 6h. Moreover, we found that the risk of death also proportionally increased for each additional hour of cold ischemia time (hazard ratio, 1.018). Thus, every additional hour of cold ischemia time must be taken into account in order to increase graft and patient survival. These findings are of practical clinical interest, as cold ischemia time is among one of the main modifiable pre-transplantation risk factors that can be minimized by improved management of the peri-transplantation period.
Background.
Kidney transplant recipients (KTRs) are still at risk of severe COVID-19 disease after SARS‑CoV‑2 vaccination, especially when they have limited antibody formation. Our aim was to ...understand the factors that may limit their humoral response.
Methods.
Our data are derived from KTRs who were enrolled in the Dutch Renal Patients COVID-19 Vaccination consortium, using a discovery cohort and 2 external validation cohorts. Included in the discovery (N = 1804) and first validation (N = 288) cohorts were participants who received 2 doses of the mRNA-1273 vaccine. The second validation cohort consisted of KTRs who subsequently received a third dose of any SARS-CoV-2 vaccine (N = 1401). All participants had no history of SARS-CoV-2 infection. A multivariable logistic prediction model was built using stepwise backward regression analysis with nonseroconversion as the outcome.
Results.
The discovery cohort comprised 836 (46.3%) KTRs, the first validation cohort 124 (43.1%) KTRs, and the second validation cohort 358 (25.6%) KTRs who did not seroconvert. In the final multivariable model‚ 12 factors remained predictive for nonseroconversion: use of mycophenolate mofetil/mycophenolic acid (MMF/MPA); chronic lung disease, heart failure, and diabetes; increased age; shorter time after transplantation; lower body mass index; lower kidney function; no alcohol consumption; ≥2 transplantations; and no use of mammalian target of rapamycin inhibitors or calcineurin inhibitors. The area under the curve was 0.77 (95% confidence interval CI, 0.74-0.79) in the discovery cohort after adjustment for optimism, 0.81 (95% CI, 0.76-0.86) in the first validation cohort, and 0.67 (95% CI, 0.64-0.71) in the second validation cohort. The strongest predictor was the use of MMF/MPA, with a dose-dependent unfavorable effect, which remained after 3 vaccinations.
Conclusions.
In a large sample of KTRs, we identify a selection of KTRs at high risk of nonseroconversion after SARS-CoV-2 vaccination. Modulation of MMF/MPA treatment before vaccination may help to optimize vaccine response in these KTRs. This model contributes to future considerations on alternative vaccination strategies.
Although previous consensus recommendations have helped define patients who would benefit from simultaneous liver–kidney transplantation (SLK), there is a current need to reassess published ...guidelines for SLK because of continuing increase in proportion of liver transplant candidates with renal dysfunction and ongoing donor organ shortage. The purpose of this consensus meeting was to critically evaluate published and registry data regarding patient and renal outcomes following liver transplantation alone or SLK in liver transplant recipients with renal dysfunction. Modifications to the current guidelines for SLK and a research agenda were proposed.
The authors report the findings of a summit meeting on simultaneous liver–kidney transplantation, present modifications to the current guidelines and propose directions for future research. See editorial by Feng and Trotter on page 2869.
Possible roles of anti-nephrin antibodies in post-transplant recurrent focal segmental glomerulosclerosis (FSGS) have been reported recently. To confirm these preliminary results, we performed a ...multi-institutional study of 22 Japanese pediatric kidney transplant recipients with FSGS including eight genetic FSGS and 14 non-genetic (presumed primary) FSGS. Eleven of the 14 non-genetic FSGS patients had post-transplant recurrent FSGS. Median (interquartile range) plasma levels of anti-nephrin antibodies in post-transplant recurrent FSGS measured using ELISA were markedly high at 899 (831, 1292) U/mL (cutoff 231 U/mL) before transplantation or during recurrence. Graft biopsies during recurrence showed punctate IgG deposition co-localized with nephrin that had altered localization with increased nephrin tyrosine phosphorylation and Src homology and collagen homology A expressions. Graft biopsies after remission showed no signals for IgG and a normal expression pattern of nephrin. Anti-nephrin antibody levels decreased to 155 (53, 367) U/mL in five patients with samples available after remission. In patients with genetic FSGS as in those with non-genetic FSGS without recurrence, anti-nephrin antibody levels were comparable to those of 30 control individuals, and graft biopsies had no signals for IgG and a normal expression pattern of nephrin. Thus, our results suggest that circulating anti-nephrin antibodies are a possible candidate for circulating factors involved in the pathogenesis of post-transplant recurrent FSGS and that this may be mediated by nephrin phosphorylation. Larger studies including other ethnicities are required to confirm this finding.
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Prediction models for post‐kidney transplantation mortality have had limited success (C‐statistics ≤0.70). Adding objective measures of potentially modifiable factors may improve prediction and, ...consequently, kidney transplant (KT) survival through intervention. The Short Physical Performance Battery (SPPB) is an easily administered objective test of lower extremity function consisting of three parts (balance, walking speed, chair stands), each with scores of 0–4, for a composite score of 0–12, with higher scores indicating better function. SPPB performance and frailty (Fried frailty phenotype) were assessed at admission for KT in a prospective cohort of 719 KT recipients at Johns Hopkins Hospital (8/2009 to 6/2016) and University of Michigan (2/2013 to 12/2016). The independent associations between SPPB impairment (SPPB composite score ≤10) and composite score with post‐KT mortality were tested using adjusted competing risks models treating graft failure as a competing risk. The 5‐year posttransplantation mortality for impaired recipients was 20.6% compared to 4.5% for unimpaired recipients (p < 0.001). Impaired recipients had a 2.30‐fold (adjusted hazard ratio aHR 2.30, 95% confidence interval CI 1.12–4.74, p = 0.02) increased risk of postkidney transplantation mortality compared to unimpaired recipients. Each one‐point decrease in SPPB score was independently associated with a 1.19‐fold (95% CI 1.09–1.30, p < 0.001) higher risk of post‐KT mortality. SPPB‐derived lower extremity function is a potentially highly useful and modifiable objective measure for pre‐KT risk prediction.
Pre–kidney transplant lower extremity function is independently associated with posttransplant mortality.
The persistent challenges of bridging healthcare disparities for African Americans (AAs) in need of kidney transplantation continue to be unresolved at the national level. This healthcare disparity ...is multifactorial: stemming from limited kidney donors suitable for AAs; inconsistent care coordination and suboptimal risk factor control; social determinants, low socioeconomic status, reduced access to care; and mistrust of clinicians and the healthcare system.
There are numerous opportunities to significantly lessen the disparities in kidney transplantation for AAs through the following measures: the adoption of new care and patient engagement models that include education, enhanced practice-level cultural sensitivity, and timely referral as well as increased research on the impact of the environment on genetic risk, and implementation of new transplantation-related policies. Key Messages: This systematic review describes pretransplant concerns related to access to kidney transplantation, posttransplant complications, and policy interventions to address the challenging issues associated with kidney transplantation in AAs.
The intrarenal resistive index is routinely measured in many renal-transplantation centers for assessment of renal-allograft status, although the value of the resistive index remains unclear.
In a ...single-center, prospective study involving 321 renal-allograft recipients, we measured the resistive index at baseline, at the time of protocol-specified renal-allograft biopsies (3, 12, and 24 months after transplantation), and at the time of biopsies performed because of graft dysfunction. A total of 1124 renal-allograft resistive-index measurements were included in the analysis. All patients were followed for at least 4.5 years after transplantation.
Allograft recipients with a resistive index of at least 0.80 had higher mortality than those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 5.20 95% confidence interval {CI}, 2.14 to 12.64; P<0.001; 3.46 95% CI, 1.39 to 8.56; P=0.007; and 4.12 95% CI, 1.26 to 13.45; P=0.02, respectively). The need for dialysis did not differ significantly between patients with a resistive index of at least 0.80 and those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 1.95 95% CI, 0.39 to 9.82; P=0.42; 0.44 95% CI, 0.05 to 3.72; P=0.45; and 1.34 95% CI, 0.20 to 8.82; P=0.76, respectively). At protocol-specified biopsy time points, the resistive index was not associated with renal-allograft histologic features. Older recipient age was the strongest determinant of a higher resistive index (P<0.001). At the time of biopsies performed because of graft dysfunction, antibody-mediated rejection or acute tubular necrosis, as compared with normal biopsy results, was associated with a higher resistive index (0.87 ± 0.12 vs. 0.78 ± 0.14 P=0.05, and 0.86 ± 0.09 vs. 0.78 ± 0.14 P=0.007, respectively).
The resistive index, routinely measured at predefined time points after transplantation, reflects characteristics of the recipient but not those of the graft. (ClinicalTrials.gov number, NCT01879124 .).
Compared with the standard open approach, multiport robotic-assisted kidney transplantation (RAKT) has emerged as a less morbid alternative. The use of a single-port robotic approach for kidney ...transplantation (KT) is presented in this study as having the potential for further reducing the morbidity of KT.
To present the technique and evaluate perioperative and short-term (≤1 yr) postoperative outcomes of single-port RAKT.
Prospective evaluation of peri- and postoperative outcomes in patients who underwent allograft KT (n = 6) or kidney autotransplantation (n = 3). The IDEAL model (www.ideal-collaboration.net/framework) for safe surgical innovation was used.
Kidney allografts from living or deceased donors were transplanted into six patients with end-stage renal disease. Single-port robotic surgery was performed through a 5-cm midline periumbilical abdominal incision with transperitoneal or extraperitoneal approaches. With similar incision and technique, the right or left kidney was removed and autotransplantation was performed in three patients.
Intra- and postoperative variables, and outcomes were assessed with a descriptive analysis.
Single-port RAKT procedures were completed successfully, with total operative and vascular anastomosis times ranging from 300 to 450 mins and from 52 to 92 mins, respectively. All six patients had excellent graft function with serum creatinine levels at the last follow-up (2 wk to 1 yr), ranging from 1.2 to 1.5 mg/dl. Renal autotransplantation was also completed successfully with a single-port robotic approach in three patients. The total operative and vascular anastomosis times ranged from 510 to 600 mins and from 65 to 83 mins, respectively. In all three cases, serum creatinine levels remained normal after the surgery and during follow-up, and all remained symptom-free at the time of this writing (4–8 mo after their surgeries).
In this initial experience, single-port RAKT is feasible with potential benefits such as offering true single-site minimally invasive surgery, extraperitoneal approach, less morbidity, and comparable short-term graft functional outcomes.
We presented the initial experience with the application of single-port robotic surgery for kidney transplantation and autotransplantation. This technique was found to be safe and effective, with promising postoperative outcomes and potentially with less morbidity.
In our first ever initial series of single-port robotic-assisted kidney transplantation including allotransplantation and autotransplantation, we demonstrated safety and feasibility of the technique, with excellent early graft function. While these early results are promising, a larger series with longer follow-up is required. If future comparative trials confirm, further minimization of the morbidity of kidney transplantation may be associated with improved recovery in terms of reduced hospitalization and/or postoperative pain.
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